Pathophysiology of diabetic hepatopathy and molecular mechanisms underlying the hepatoprotective effects of phytochemicals

Abstract

Patients with diabetes are at risk for liver disorders including glycogen hepatopathy, non-alcoholic fatty liver disease, cirrhosis, and hepatic fibrosis. The pathophysiological mechanisms behind diabetic hepatopathy are complex, some of them include fatty acid accumulation, increased reactive oxygen species, increased advanced glycation end-products, hyperactivity of polyol pathways, increased apoptosis and necrosis, and promotion of fibrosis. A growing number of studies have shown that herbal extracts and their active phytochemicals have antihyperglycemic properties and beneficial effects on diabetic complications. The current review, for the first time, focused on herbal agents that showed beneficial effects on diabetic hepatopathy. For example, animal studies have shown that Moringa oleifera and Morus alba improve liver function in both type-1 and type-2 diabetes. Also, evidence from clinical trials suggests that Boswellia serrata, Juglans regia, Melissa officinalis, Portulaca oleracea, Silybum marianum, Talapotaka Churna, and Urtica dioica reduce serum liver enzymes in diabetic patients. The main active ingredient of these plants to protect the liver seems to be phenolic compounds such as niazirin, chlorogenic acid, resveratrol, etc. Mechanisms responsible for the hepatoprotective activity of herbal agents include improving glucose metabolism, restoring adipokines levels, antioxidant defense, and anti-inflammatory activity. Several signaling pathways are involved in hepatoprotective effects of herbal agents in diabetes, such as phosphoinositide 3-kinase, adenosine monophosphate-activated protein kinase, mitogen-activated protein kinase, and c-Jun NH2-terminal kinase.

Keywords: Diabetes; Liver; Mechanisms; Pathophysiology; Phytochemicals; Plants.